Kinetic analysis of a model of the sarcoplasmic reticulum Ca-ATPase, with variable stoichiometry, which enhances the amount and the rate of Ca transport

The sarcoplasmic reticulum (SR) Ca-dependent adenosinetriphosphatase (Ca-AT Pase) actively transports Ca2+ from the myoplasm to the SR lumen. Under opt imal conditions a 2:1 stoichiometry of Ca transport/ATP hydrolysis has been observed, but lower stoichiometries have been reported under several circu mstances. A lower stoichiometry under conditions of high Ca2+ load, althoug h thermodynamically less efficient: could in theory increase the rate and t he maximal amount of Ca uptake. We analysed, by computing simulation, the t ransient kinetics of a model of the SR Ca-ATPase with variable stoichiometr y. The model is based on current experimental reports and includes the most relevant properties of the system. The results show an acceleration in the rate of Ca uptake, an increase in the net Ca transport, and an increase in the rate of [Ca2+] reduction in the medium, which might be physiologically useful to increase the rate of Ca pumping at high Ca load of the sarcoplas mic reticulum. (C) 2001 Academic Press.